Cerebral microvessels will be injured by a variety of means and the resultant platelet aggregation and/or vasoconstriction will be monitored in vivo. The sensitivities of injured microvessels to known vasoactive agents will also be examined to see whether abnormal sensitivity is observed. Drug effects on these parameters will be investigated with a view toward finding preventative agents and also to explaining the mechanisms responsible for the untoward microvascular reactions. Normal animals, diabetic animals and hypertensive animals will be investigated. Studies of several extracerebral microvascular beds and several species will be carried out to determine how generalizable are our results. In vitro studies of platelet aggregability, ultrastructural studies of platelets and microvessel, and pharmacologic studies of vessels and platelets will be conducted to gather data that may explain the phenomena observed in vivo.